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1.
J Fish Biol ; 104(5): 1411-1422, 2024 May.
Article in English | MEDLINE | ID: mdl-38351593

ABSTRACT

The age and daily growth of fish are registered through the deposition of increments in their otoliths, which are concretions formed by the precipitation of substances present in the endolymphatic fluid, mainly calcium carbonate (CaCO3). Faced with the need to fill some of the gaps in the knowledge on the occurrence and duration of the initial stages of snapper species' life cycles in the Abrolhos Bank, this study aimed to describe the growth rates, age, and period of pelagic larval duration (PLD) of three snapper species during the larval pre-settlement phase, in the Abrolhos Bank region. The post-larvae were captured using light traps. Otoliths were removed from 117 samples of snapper species; however, only 69 were viable for age estimation, of which 15 were Lutjanus analis, 25 were Lutjanus jocu, and 29 were Lutjanus synagris. Together, the samples presented individuals with total lengths ranging from 16.14 to 24.76 mm and ages from 21 to 39 days. Settlement marks were found for all three species, and the average PLD was ~25 days. The somatic growth of the snapper species was positively correlated with otolith growth. L. jocu presented the greatest daily growth compared to the other species. The three species use the Abrolhos Bank as a larval settlement site, demonstrating plasticity by using different habitats throughout their lives.


Subject(s)
Larva , Otolithic Membrane , Animals , Larva/growth & development , Otolithic Membrane/growth & development , Otolithic Membrane/chemistry , Perciformes/growth & development , Parks, Recreational , Perches/growth & development , Perches/physiology
2.
SAGE Open Med ; 12: 20503121241228446, 2024.
Article in English | MEDLINE | ID: mdl-38322582

ABSTRACT

Acute kidney injury is a prevalent disease in hospitalized patients and is continuously increasing worldwide. Various efforts have been made to define and classify acute kidney injury to understand the progression of this disease. Furthermore, deviations from structure and kidney function and the current diagnostic guidelines are not adequately placed due to baseline serum creatinine values, which are rarely known and estimated based on glomerular function rate, resulting in misclassification of acute kidney injury staging. Hence, the current guidelines are still developing to improve and understand the clinical implications of risk factors and earlier predictive biomarkers of acute kidney injury. Yet, studies have indicated disadvantages and limitations with the current acute kidney injury biomarkers, including lack of sensitivity and specificity. Therefore, the present narrative review brings together the most current evidenced-based practice and literature associated with the limitations of the gold standard for acute kidney injury diagnoses, the need for novel acute kidney injury biomarkers, and the process for biomarkers to be qualified for diagnostic use under the following sections and themes. The introduction section situates the anatomy and normal and abnormal kidney functions related to acute kidney injury disorders. Guidelines in providing acute kidney injury definitions and classification are then considered, followed by a discussion of the disadvantages of standard markers used to diagnose acute kidney injury. Characteristics of an ideal acute kidney injury biomarker are discussed concerning sensitivity, specificity, and anatomic location of injury. A particular focus on the role and function of emerging biomarkers is discussed in relation to their applications and significance to the prognosis and severity of acute kidney injury. Findings show emerging markers are early indicators of acute kidney injury prediction in different clinical settings. Finally, the process required for a biomarker to be applied for diagnostic use is explained.

3.
Heliyon ; 9(10): e20662, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37867831

ABSTRACT

The WASF3 gene promotes cancer cell invasion and metastasis, and genetic inactivation leads to suppression of metastasis. To identify small molecules that might interfere with WASF3 function, we performed an in silico docking study to the regulatory pocket of WASF3 using the National Cancer Institute (NCI) diversity set VI small molecule library. Compounds that showed the maximum likelihood of interaction with WASF3 were screened for their effect on cell movement in breast and prostate cancer cells, a well-established predictor of invasion and metastasis. Three hit compounds were identified that affected cell movement, and the same compounds also suppressed cell migration and invasion in vitro in both MDA-MB-231 breast cancer cells and Du145 prostate cancer cells. Using a zebrafish metastasis assay, one of these compounds, NSC670283, showed significant suppression of metastasis in vivo while not affecting cell proliferation. NSC670283 showed a consistent effect on suppression of invasion and metastasis, and cellular temperature shift assays provided support for physical interaction with WASF3. In addition, suppression of cell movement and invasion was accompanied by a decrease in actin filament polymerization. The data in this study suggest that these small molecules inhibit cancer cell invasion and metastasis, and to our knowledge, it is the first identification of a small molecule that can potentially inhibit WASF3-directed metastasis, laying the foundation for medicinal chemistry approaches to enhance the potency of the identified compounds.

4.
J Telemed Telecare ; : 1357633X231194381, 2023 Aug 24.
Article in English | MEDLINE | ID: mdl-37615156

ABSTRACT

Although the use of audiovisual telemedicine has grown in recent years especially during recent COVID-19-related lockdowns, evidence shows there is still a lack of tools that can be used for the assessment of telemedicine encounters. The few validated questionnaires that are available for assessing telemedicine encounters are not often used. Non-validated questionnaires dominate research, leading to results that cannot be compared or extrapolated to other research or medical sites. Development of standard measures for the assessment of telemedicine encounters has been advocated by stakeholders. The objective of this study is to provide a comprehensive set of measures by developing a conceptual approach and a preliminary Telemedicine Assessment Toolkit (TAT) for the assessment of audiovisual telemedicine encounters. A two-step conceptual approach was used to identify potential domains and sub-domains by qualitative analysis of a pool of questions from studies published from 2016 to 2021. Questions were adopted from validated questionnaires or generated to represent the underlying concept of each sub-domain, resulting in a core block of comprehensive questions. A toolkit is proposed with question-measures that cover the sub-domains relevant to the assessment of telemedicine encounters. This study recommended 11 domains to be used for the assessment of telemedicine encounters: "usability," "patient satisfaction," "patient-provider interaction," "patient perspectives," "telemedicine readiness," "qualitative feedback," "comparison to standard (in-person) care," "privacy," "technology," "patient feeling," and "patient costs." Of the 11 domains, 26 underlying sub-domains were created. From the subdomains, a 30-question core block was proposed. The core-block together with a precursor block aimed to retrieve demographic/patient characteristics and, together with a customizable clinical outcomes block, complete the comprehensive toolkit. The toolkit, upon testing and validation, would enable researchers and system owners to assess patient-oriented aspects of audiovisual telemedicine encounters more accurately and accelerate the adoption of common audiovisual telemedicine assessment measures.

5.
Clin Oral Investig ; 27(5): 1801-1814, 2023 May.
Article in English | MEDLINE | ID: mdl-36757462

ABSTRACT

OBJECTIVE: To assess the accuracy of cone-beam computed tomography (CBCT) for determining gingival thickness. MATERIAL AND METHODS: Searches were undertaken in PubMed/MEDLINE, EMBASE, LILACS, Web of Science, Scopus, LIVIVO, and gray literature (Google Scholar and ProQuest) for studies considered eligible according to the following criteria: cross-sectional observational studies, which compared CBCT accuracy with that of transgingival probing when determining gingival thickness, in adult patients with good periodontal health. No language or time restrictions were applied in this systematic review. The risk of bias was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for analytical cross-sectional studies. RESULTS: Six articles were included for qualitative synthesis, involving a pooled sample of 132 patients with a mean age of 29 years (18-51 years). Of these 6 studies, 5 were eligible for quantitative analysis. The meta-analysis showed no statistically significant difference between CBCT and transgingival probing measures of gingival tissue (mean difference of 0.10 (95% CI-0.17-0.38). No significant level of heterogeneity was detected (Tau2-P = 0.0662; I2 = 0%; H2-P = 1.000; Q-P = 1.134). According to the GRADE criterion, confidence in the cumulative evidence was considered low. CONCLUSIONS: CBCT is an accurate method for determining gingival tissue thickness, comparable to the reference standard (transgingival probing). CLINICAL RELEVANCE: CBCT could be considered for gingival thickness measurement when bone thickness is also needed, and thereby aid in the assessment of gingival biotype without the discomfort and anesthesia needed in transgingival probing. TRIAL REGISTRATION: This protocol was registered at the PROSPERO database (International Prospective Register of Systematic Review) under registration number CRD42022326970. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022326970 .


Subject(s)
Cone-Beam Computed Tomography , Gingiva , Adult , Humans , Cross-Sectional Studies , Gingiva/diagnostic imaging , Cone-Beam Computed Tomography/methods , Physical Examination
6.
Public Health Rep ; 138(2): 315-322, 2023.
Article in English | MEDLINE | ID: mdl-36354213

ABSTRACT

OBJECTIVES: The COVID-19 pandemic has disrupted the social life, work environment, and well-being of millions of people. We examined COVID-19's impact on National Institutes of Health (NIH)-funded extramural principal investigators (PIs) affiliated with public health and preventive medicine departments across the country and their projects; assessed PIs' confidence in achieving project goals; and investigated the role of age, sex, experience, and team size on PIs' confidence in achieving project goals during the pandemic. METHODS: We sent an anonymous online survey in January 2021 to 1076 extramural PIs affiliated with public health and preventive medicine departments at US institutions; 133 (12.4%) responded. We examined the impact of COVID-19 on the PIs, their project team operations, and their confidence that project objectives would be met, using Likert scales based on age, sex, team size, and PI experience. RESULTS: Of 126 PIs, 94 (74.6%) felt that their day-to-day professional life was impacted a lot or a great deal by COVID-19. More female PIs than male PIs reported that their level of stress changed because of the COVID-19 pandemic. Of 125 PIs, 67 (53.6%) made major adjustments to research operations, 46 (36.8%) made minor adjustments, 5 (4.0%) halted research, and 7 (5.6%) reported not being affected. Of 123 PIs, 89 (72.4%) reported not using NIH COVID-19 accommodations. PIs who led projects 4 or 5 times felt more confident about meeting their research objectives than PIs who led projects 2 or 3 times. CONCLUSIONS: Future studies should investigate how to develop more engaging support and communication strategies to assist NIH researchers in mitigating the effects of pandemics or large-scale emergencies.


Subject(s)
Biomedical Research , COVID-19 , United States/epidemiology , Humans , Male , Female , Pandemics/prevention & control , COVID-19/epidemiology , Surveys and Questionnaires , National Institutes of Health (U.S.)
7.
Article in English | MEDLINE | ID: mdl-35396197

ABSTRACT

OBJECTIVE: This systematic review was undertaken to determine the risk of oral cancer in patients with chronic graft-vs-host disease (cGvHD). STUDY DESIGN: The search was conducted in 6 electronic databases (PubMed/MEDLINE, EMBASE, LILACS, Web of Science, Scopus, and LIVIVO) and gray literature (Google Scholar, Open Gray, and ProQuest) for studies published up to November 2021. RESULTS: Of the 13 cohorts included in qualitative synthesis, 9 were eligible for the quantitative analysis. The meta-analysis showed that the presence of cGvHD increased the risk of developing oral cancer (risk ratio [RR] = 2.78; 95% CI, 1.27-6.08; I2 = 46%; P = .01). A subgroup meta-analysis revealed a higher risk of oral cancer in Asian samples exposed to cGvHD (RR = 2.50; 95% CI, 1.54-4.04; I2 = 0%; P = .0002), which was not seen in the pooled analysis of European samples (P = .24). The overall methodological quality of most studies included was "good." The cumulative evidence (Grading of Recommendations Assessment, Development and Evaluation) was considered moderate and of very low confidence for Asian and European studies, respectively. CONCLUSIONS: Patients with cGvHD resulting from allogenic hematopoietic stem cell transplantation run an increased risk of developing oral cancer. Hence, it is recommended that patients with cGvHD be monitored to allow for the early detection and treatment of secondary malignant disease.


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Mouth Neoplasms , Graft vs Host Disease/complications , Hematopoietic Stem Cell Transplantation/adverse effects , Humans
8.
Antibiotics (Basel) ; 12(1)2022 Dec 23.
Article in English | MEDLINE | ID: mdl-36671222

ABSTRACT

A clinical-epidemiological score to predict CR-GNB sepsis to guide empirical antimicrobial therapy (EAT), using local data, persists as an unmet need. On the basis of a case-case-control design in a prospective cohort study, the predictive factors for CR-GNB sepsis were previously determined as prior infection, use of mechanical ventilation and carbapenem, and length of hospital stay. In this study, each factor was scored according to the logistic regression coefficients, and the ROC curve analysis determined its accuracy in predicting CR-GNB sepsis in the entire cohort. Among the total of 629 admissions followed by 7797 patient-days, 329 single or recurrent episodes of SIRS/sepsis were enrolled, from August 2015 to March 2017. At least one species of CR-GNB was identified as the etiology in 108 (33%) episodes, and 221 were classified as the control group. The cutoff point of ≥3 (maximum of 4) had the best sensitivity/specificity, while ≤1 showed excellent sensitivity to exclude CR-GNB sepsis. The area under the curve was 0.80 (95% CI: 0.76-0.85) and the number needed to treat was 2.0. The score may improve CR-GNB coverage and spare polymyxins with 22% (95% CI: 17-28%) adequacy rate change. The score has a good ability to predict CR-GNB sepsis and to guide EAT in the future.

9.
Genomics ; 112(2): 1167-1172, 2020 03.
Article in English | MEDLINE | ID: mdl-31276752

ABSTRACT

LGI1 mutations predispose to a rare epilepsy syndrome and when inactivated in mice leads to early onset seizures and premature death. Histopathology of the mature brain soon after birth shows cortical dysplasia in Lgi1 null mice with hypercellularity in the outer cortical layers. Here we show extensive gene expression changes in neuronal precursor cells from Lgi1 null mice compared with wild type mice. The most significantly dysregulated pathway involves canonical axon guidance signaling with multiple networks involved in cell movement, adhesion and invasion related to actin cytoskeleton reorganization. The Lgi1 null NPCs show increased cell motility in vitro compared with normal counterparts. Dysregulation of genes critical to cell movement/migration and critical transcription factors involved in early neuronal development is a prominent feature. These studies provide a critical mechanistic link to the observation of increased cellularity in the outer layers of the developing cortex in Lgi1 null mice.


Subject(s)
Axon Guidance , Intracellular Signaling Peptides and Proteins/genetics , Neural Stem Cells/metabolism , Actin Cytoskeleton/metabolism , Animals , Cell Movement , Cells, Cultured , Intracellular Signaling Peptides and Proteins/metabolism , Mice , Neural Stem Cells/cytology , Neural Stem Cells/physiology , Transcription Factors/genetics , Transcription Factors/metabolism
10.
ROBRAC ; 28(84): 1-4, jan./mar. 2019. Ilus, Tab
Article in Portuguese | LILACS | ID: biblio-1049218

ABSTRACT

Objetivo: Avaliar a acurácia, sensibilidade e especificidade de diferentes filtros do software Cliniview™ (versão 10.1) em radiografias periapicais digitais na detecção de fraturas radiculares verticais em dentes unirradiculares. Material e Métodos: Foram utilizados 31 dentes humanos recém-extraídos divididos em dois grupos: controle (CTL) e fraturado (FTR), constituídos por 15 e 16 dentes, respectivamente. Realizou-se o tratamento endodôntico dos dentes para posterior desobturação de 2/3 da raiz e confecção dos pinos metálicos. Após cimentação dos pinos, as raízes dos dentes grupo FTR foram fraturadas na máquina de ensaio (Instron). As radiografias periapicais digitais foram obtidas em todos os dentes com sistema digital Express™. As radiografias originais e com aplicação dos filtros (inversão na escala de cinza, hot, nitidez 1, vertical e vertical + horizontal) foram salvas e avaliadas por dois especialistas. Após as análises, foram calculados os valores de sensibilidade, especificidade, preditivo positivo, preditivo negativo e acurácia da radiografia periapical digital com e sem a aplicação dos filtros. Resultados: Considerando os dois examinadores, os maiores valores de acuraria, sensibilidade e especificidade para as imagens originais foram de 85,2%, 100% e 95,2% respectivamente. Para as radiografias com aplicação de filtro, os maiores valores de acurácia, sensibilidade e especificidade foram de 82,6%, 71,4% e 87,5%, respectivamente. Conclusão: O uso de filtros não aumentou os valores de acurácia, sensibilidade e especificidade das radiografias periapicais digitais para a detecção das fraturas radiculares verticais. De fato, pelo contrário, em alguns casos, o diagnóstico piorou.


Objective: To evaluate the accuracy, sensitivity, and specificity of different Cliniview™ (version 10.1) software filters in digital periapical radiographs for the detection of vertical root fractures in single-rooted teeth. Materials and Methods: Thirty-one human teeth freshly extracted were divided into two groups: control (CTL) and fractured (FTR), constituted by 15 and 16 teeth respectively. The endodontic treatment of the teeth was performed and followed by desobturation of ⅔ of the root canal and the metallic posts confection. After the cementation of the posts, the fractures were made using the universal test machine (Instron) only in the FTR group. The digital periapical radiographs were performed in all the teeth using the ExpressTM digital system. The original radiographs and the ones with applied filters (gray scale, hot, sharpness 1, vertical and vertical + horizontal) were saved and evaluated by two specialists. After the analysis, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the digital periapical radiographs with and without the application of filters were calculated. Results: Taking into consideration the two examiners, the highest accuracy, sensitivity and specificity values for the original images were 85,2%, 100% and 95,2% respectively. For the radiographs with applied filters, the highest accuracy, sensitivity and specificity values found were of 82,6%, 71,4% and 87,5%, respectively. Conclusion: The use of filters did not increase the accuracy, sensitivity and specificity values of the digital periapical radiographs for the detection of VRF. In fact, on the contrary, for some cases, the diagnosis became worse.

11.
Genesis ; 57(2): e23268, 2019 02.
Article in English | MEDLINE | ID: mdl-30489685

ABSTRACT

Constitutional mutations in Leucine-rich glioma inactivated 1 (LGI1) predispose to an autosomal dominant epilepsy syndrome in humans and germline inactivation of LGI1 in mice leads to early onset seizures. LGI1 is highly expressed in the regions involved in neuronal stem cell generation and migration and detailed analysis of the brains in these mice reveals a subtle cortical dysplasia characterized by hypercellularity in the outer cortical layers. To investigate the cellular origin for this cortical dysplasia, we created mice that allow cell-specific, conditional inactivation of LGI1. Exons 3-4, which contain critical motifs for LGI1 function, were targeted for deletion and, using a CMV-cre mouse strain, global inactivation of LGI1 led to early onset seizures and the same cortical dysplasia seen in the constitutionally null mice. Similarly, inactivation of LGI1 in cells expressing Nestin, expressed primarily in neuronal precursor cells, led to early onset seizures and cortical dysplasia. In contrast, targeting inactivation of LGI1 in cells expressing Gfap, Camk2a, and parvalbumin, did not lead to cortical dysplasia. This strain of mouse, therefore, allows for a more refined investigation of the cell types involved in the cortical dysplasia seen following inactivation of LGI1 and potentially a better understanding of the molecular mechanisms behind LGI1-induced epilepsy.


Subject(s)
Malformations of Cortical Development/genetics , Neural Stem Cells/metabolism , Proteins/genetics , Animals , Brain/cytology , Brain/growth & development , Brain/metabolism , Intracellular Signaling Peptides and Proteins , Loss of Function Mutation , Mice
12.
Genomics ; 111(6): 1566-1573, 2019 12.
Article in English | MEDLINE | ID: mdl-30439482

ABSTRACT

Constitutive activation of FGFR1 as a result of chromosome translocations is responsible for the development of a hematopoietic stem cell disorder that progresses to AML. We have developed a syngeneic mouse model of BCR-FGFR1 driven AML and used RNASeq to define gene expression signatures associated with disease progression. The development of the leukemic stem cells (LSC) is associated with a profound downregulation of specific transcription factors that normally maintain stem cell quiescence as well as cell adhesion and motility gene sets related to confinement to the stem cell niche. A prominent feature of the LSCs is the upregulation of genes involved in T-cell function, activation, migration and development. Despite this apparent T-cell priming in the LSCs, however, the majority of these genes are subsequently inactivated in the leukemic blast cells that derive from them. These studies provide insights into the molecular etiology of development and progression of FGFR1 driven AML.


Subject(s)
Leukemia, Myeloid, Acute , Neoplasm Proteins , Neoplasms, Experimental , Neoplastic Stem Cells , Receptor, Fibroblast Growth Factor, Type 1 , Signal Transduction/genetics , Animals , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/metabolism , Leukemia, Myeloid, Acute/pathology , Mice , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Neoplasms, Experimental/genetics , Neoplasms, Experimental/metabolism , Neoplasms, Experimental/pathology , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/pathology , Receptor, Fibroblast Growth Factor, Type 1/genetics , Receptor, Fibroblast Growth Factor, Type 1/metabolism
13.
Cancer Res ; 78(13): 3522-3531, 2018 07 01.
Article in English | MEDLINE | ID: mdl-29735550

ABSTRACT

The development of myeloid and lymphoid neoplasms related to overexpression of FGFR1 kinases as a result of chromosome translocations depends on the promotion of a stem cell phenotype, suppression of terminal differentiation, and resistance to apoptosis. These phenotypes are related to the stem cell leukemia/lymphoma syndrome (SCLL), which arises through the effects of the activated FGFR1 kinase on gene transcription, which includes miRNA dysregulation. In a screen for miRNAs that are directly regulated by FGFR1, and which stimulate cell proliferation and survival, we identified miR-339-5p, which is highly upregulated in cells carrying various different chimeric kinases. Overexpression of miR-339-5p in SCLL cell types enhances cell survival and inhibition of its function leads to reduced cell viability. miR-339-5p overexpression protects cells from the consequences of FGFR1 inactivation, promoting cell-cycle progression and reduced apoptosis. Transient luciferase reporter assays and qRT-PCR detection of endogenous miR-339-5p expression in stably transduced cell lines demonstrated that BCR-FGFR1 can directly regulate miR-339-5p expression. This correlation between miR-339-5p and FGFR1 expression is also seen in primary human B-cell precursor acute lymphoblastic leukemia. In a screen to identify targets of miR-339-5p, we identified and verified the BCL2L11 and BAX genes, which can promote apoptosis. In vivo, SCLL cells forced to overexpress miR-339-5p show a more rapid onset of disease and poorer survival compared with parental cells expressing endogenous levels of miR-339-5p. Analysis of human primary B-cell precursor ALL shows a significant higher expression of miR339-5p compared with the two cohorts of CLL patient samples, suggesting direct roles in disease progression and supporting the evidence generated in mouse models of SCLL.Significance: Proapoptiotic genes that are direct targets of miR-339-5p significantly influence promotion and aggressive development of leukemia/lymphomas associated with FGFR1 overexpression. Cancer Res; 78(13); 3522-31. ©2018 AACR.


Subject(s)
Bcl-2-Like Protein 11/genetics , Leukemia/genetics , Lymphoma/genetics , MicroRNAs/metabolism , bcl-2-Associated X Protein/genetics , Animals , Bcl-2-Like Protein 11/metabolism , Cell Line, Tumor/transplantation , Cell Survival/genetics , Chromosomes, Human, Pair 8/genetics , Disease Models, Animal , Down-Regulation , Female , HEK293 Cells , Hematopoietic Stem Cells/pathology , Humans , Leukemia/pathology , Lymphoma/pathology , Mice , Mice, Inbred BALB C , NIH 3T3 Cells , Oncogene Proteins, Fusion/metabolism , Receptor, Fibroblast Growth Factor, Type 1/genetics , Receptor, Fibroblast Growth Factor, Type 1/metabolism , Syndrome , Translocation, Genetic , bcl-2-Associated X Protein/metabolism
14.
Oncogene ; 37(14): 1926-1938, 2018 04.
Article in English | MEDLINE | ID: mdl-29367757

ABSTRACT

MicroRNAs (miRNAs) have pathogenic roles in the development of a variety of leukemias. Here we identify miRNAs that have important roles in the development of B lymphomas resulting from the expression of the chimeric BCR-FGFR1 kinase. The miR-17/92 cluster was particularly implicated and forced expression resulted in increased cell proliferation, while inhibiting its function using miRNA sponges reduced cell growth and induced apoptosis. Cells treated with the potent BGJ389 FGFR1 inhibitor led to miR-17/92 downregulation, suggesting regulation by FGFR1. Transient luciferase reporter assays and qRT-PCR detection of endogenous miR-17/92 expression in stable transduced cell lines demonstrated that BCR-FGFR1 can regulate miR-17/92 expression. This positive association of miR-17/92 with BCR-FGFR1 was also confirmed in primary mouse SCLL tissues and primary human CLL samples. miR-17/92 promotes cell proliferation and survival by targeting CDKN1A and PTEN in B-lymphoma cell lines and primary tumors. An inverse correlation in expression levels was seen between miR-17/92 and both CDKN1A and PTEN in two cohorts of CLL patients. Finally, in vivo engraftment studies demonstrated that manipulation of miR-17/92 was sufficient to affect BCR-FGFR1-driven leukemogenesis. Overall, our results define miR-17/92 as a downstream effector of FGFR1 in BCR-FGFR1-driven B-cell lymphoblastic leukemia.


Subject(s)
Lymphoma/genetics , MicroRNAs/genetics , Oncogene Proteins, Fusion/genetics , Proto-Oncogene Proteins c-bcr/genetics , Receptor, Fibroblast Growth Factor, Type 1/genetics , Animals , Cell Line, Tumor , Cell Proliferation/genetics , Female , Gene Expression Regulation, Neoplastic , HEK293 Cells , Humans , Lymphoma/pathology , Mice , Mice, Inbred BALB C , Multigene Family/physiology , Syndrome
15.
Anticancer Drugs ; 28(2): 142-152, 2017 02.
Article in English | MEDLINE | ID: mdl-27754993

ABSTRACT

YM155 (sepantronium bromide) has been evaluated in clinical trials as a survivin suppressant, but despite positive signals from early work, later studies were negative. Clarification of the mechanism of action of YM155 is important for its further development. YM155 affects cells in a cell cycle-specific manner. When cells are in G1, YM155 prevented their progression through the S phase, leaving the cells at G1/S when exposed to YM155. Passage through mitosis from G2 is also defective following YM155 exposure. In this study, YM155 did not behave like a typical DNA intercalator in viscosity, circular dichroism, and absorption spectroscopy studies. In addition, molecular modeling experiments ruled out YM155 DNA interaction to produce DNA intercalation. We show that YM155 inhibited topoisomerase 2α decatenation and topoisomerase 1-mediated cleavage of DNA, suggesting that YM155 inhibits the enzyme function. Consistent with these findings, DNA double-strand break repair was also inhibited by YM155.


Subject(s)
Antineoplastic Agents/pharmacology , Imidazoles/pharmacology , Naphthoquinones/pharmacology , Topoisomerase Inhibitors/pharmacology , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/enzymology , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , DNA Breaks , DNA Repair , DNA Replication/drug effects , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/enzymology , Lung Neoplasms/genetics , Lung Neoplasms/pathology
16.
Interface comun. saúde educ ; 20(59): 981-991, oct.-dic. 2016.
Article in Portuguese | LILACS | ID: lil-796310

ABSTRACT

Situando-nos no cruzamento entre as áreas da saúde e educação, propomos refletir sobre formação no/para o SUS a partir de nossas experiências junto à Rede Cegonha, no Ministério da Saúde, especificamente no acompanhamento da implantação dos Centros de apoio ao desenvolvimento de boas práticas na gestão e atenção obstétrica e neonatal. Entendendo o campo da saúde como um território de ensino (formatações pedagógico-corporais) e de aprendizagens (experimentação de formas singulares de práticas de saúde), pensamos que a qualificação do cuidado em saúde (nesse caso particular, de mulheres e crianças) passa pela experimentação de um referencial ético-político-pedagógico que se desdobra em diretrizes formativas cuja potência parece se situar na gestação de um certo modo de fazer-saber-produzir formação no SUS que se tece na indissociabilidade entre trabalho-formação-intervenção-gestão.


We aim to reflect on the education in/for the SUS, as we stand at the crossroads between the health and education fields. In order to do so, we follow our own experiences with “Rede Cegonha” (Maternal care program called Stork Network), in the Ministry of Health, especially when it comes to monitoring the implementation of Support Centers for the Development of Good Practices in Management and in Obstetric and Neonatal Care. We think that health care improvement (in this particular case, for women and children) depends on experiencing an ethical-political-pedagogical framework, since we understand the health field as a teaching (pedagogic-body format) and learning field (experimentation of singular forms of health practices). Such framework unfolds into educational guidelines whose potential seems to lie on developmental way to make, know and produce education within SUS, and it means having work-education-intervention-management all together as inseparable actions.


Al situarnos en el cruce entre las áreas de salud y educación, proponemos reflexionar sobre la formación en el/para el SUS (Sistema Brasileño de Salud) a partir de nuestras experiencias junto a la Red Cigüeña, en el Ministerio de la Salud, específicamente en el acompañamiento de la implantación de los Centros de Apoyo al Desarrollo de Buenas Prácticas en la Gestión y Atención Obstétrica y Neonatal. Al comprender el campo de la salud como un territorio de enseñanza (formateos pedagógico corporales) y de aprendizajes (experimentación de formas singulares de prácticas de salud), pensamos que la calificación del cuidado en salud (en este caso particular, de mujeres y niños) pasa por la experimentación de un referencial ético, político y pedagógico que se desdobla en directrices formativas cuya potencia parece situarse en la gestación de un cierto modo de hacer-saber-producir formación en el SUS que se teje a partir de la indisociabilidad entre trabajo, formación, intervención y gestión.


Subject(s)
Unified Health System , Public Health , Education, Continuing , Maternal-Child Health Services , Health Workforce
17.
PLoS One ; 11(9): e0163698, 2016.
Article in English | MEDLINE | ID: mdl-27681225

ABSTRACT

Assessing the parental genetic differences and their subsequent prediction of progeny performance is an important first step to assure the efficiency of any breeding program. In this study, we estimate the genetic divergence in Eucalyptus camaldulensis based on the morphological traits of 132 progenies grown in a savanna biome. Thus, a field experiment was performed using a randomized block design and five replications to compare divergences in total height, commercial height, diameter at breast height, stem form and survival rate at 48 months. Tocher's clustering method was performed using the Mahalanobis and Euclidian distances. The Mahalanobis distance seemed more reliable for the assessed parameters and clustered all of the progenies into fourteen major groups. The most similar progenies (86 accessions) were clustered into Group I, while the most dissimilar (1 progeny) represented Group XIV. The divergence analysis indicated that promising crosses could be made between progenies allocated in different groups for high genetic divergence and for favorable morphological traits.

18.
Tumour Biol ; 36(12): 9717-22, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26152289

ABSTRACT

Higher tumor size correlates with poor prognosis and is an independent predictive survival factor in oral squamous cell carcinoma (OSCC) patients. However, the molecular events underlining OSCC tumor evolution are poorly understood. We aimed to investigate if large OSCC tumors show different cell cycle gene transcriptional signature compared to small tumors. Seventeen fresh OSCC tumor samples with different tumor sizes (T) were included in the study. Tumors were from the tongue or from the floor of the mouth, and only three patients were nonsmokers. Samples were categorized according to clinical tumor size in tumors ≤2 cm (T1, n = 5) or tumors >2 cm (T2, n = 9; T3, n = 2; T4, n = 1). The group of tumors ≤2 cm was considered the reference group, while the larger tumors were considered the test group. We assessed the expression of 84 cell cycle genes by qRT-PCR array and normalized it to the expression of two housekeeping genes. Results were analyzed according to the formula 2(^-DeltaCt). A five-fold change cutoff was used, and p values <0.05 were considered statistically significant. Ki-67 immunohistochemistry was performed to estimate cell proliferation index. Twenty-nine genes were downregulated in the test group (larger tumors) compared to the reference group (smaller tumors). Among these genes, 13 reached statistical significance: ANAPC4, CUL1, SUMO1, KPNA2, MAD2L2, CCNG2, E2F4, NBN, CUL2, PCNA, TFDP1, KNTC1, and ATR. Ki-67 labeling index was similar in both tumor groups. Our findings suggest that the transcriptional activity of specific cell cycle genes varies according to the size of OSCC tumor, which probably reflects tumor molecular evolution and adaptation to the microenvironment.


Subject(s)
Carcinoma, Squamous Cell/genetics , Gene Expression Profiling , Mouth Neoplasms/genetics , Transcription, Genetic , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/pathology , Cell Cycle/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Male , Middle Aged , Mouth Neoplasms/pathology , Neoplasm Proteins/biosynthesis , Prognosis , Tumor Microenvironment/genetics
19.
Photodiagnosis Photodyn Ther ; 12(3): 401-7, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26093167

ABSTRACT

BACKGROUND: The aim of this study was to evaluate the antimicrobial effect of photodynamic therapy (PDT) in carious lesions in vivo by culture and real-time PCR methods. METHODS: Ten teeth with deep active carious lesions were selected and five portions of carious dentin were removed for each tooth. Two increments were used as control, to represent the superficial and deep dentin, respectively. Methylene blue at 100mg/L was placed in contact with the cavity for 5min, before being irradiated with a halogen light source for 1min. Then, after PDT, other three portions were removed. The samples were processed in laboratory and the number of viable cfu was obtained. The real-time PCR analyses were performed in two increments of carious dentin, removed before and after PDT. The Streptococcus mutans DNA was isolated from carious dentin samples and amplification and detection of DNA were performed with real-time PCR. The cavities were then restored with glass-ionomer cement. RESULTS: Using conventional culture methods, the results demonstrated that viable bacteria were significantly reduced in all of the agar plates following photosensitization. No difference was found between both groups regarding S. mutans DNA quantification by real-time PCR. CONCLUSION: Although PDT may not affect the number of S. mutans DNA copies immediately after the treatment, clear reduction of the number of cfu was found. Despite its promising use for eliminating bacteria in dental caries treatment, further studies are necessary to establish an effective clinical protocol for the PDT.


Subject(s)
Dental Caries/drug therapy , Methylene Blue/therapeutic use , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , Streptococcus mutans/drug effects , Child , Child, Preschool , DNA, Bacterial , Dentin , Female , Humans , Male , Microbial Viability , Real-Time Polymerase Chain Reaction
20.
Brain Pathol ; 25(5): 587-97, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25346110

ABSTRACT

LGI1 mutations lead to an autosomal dominant form of epilepsy. Lgi1 mutant null mice develop seizures and show abnormal neuronal excitability. A fine structure analysis of the cortex in these mice demonstrated a subtle cortical dysplasia, preferentially affecting layers II-IV, associated with increased Foxp2 and Cux1-expressing neurons leading to blurring of the cortical layers. The hypercellularity observed in the null cortex resulted from an admixture of highly branched mature pyramidal neurons with short and poorly aligned axons as revealed by Golgi staining and immature small neurons with branched disoriented dendrites with reduced spine density and undersized, morphologically altered and round-headed spines. In vitro, hippocampal neurons revealed poor neurite outgrowth in null mice as well as reduced synapse formation. Electron microscopy demonstrated reduced spine-localized asymmetric (axospinous) synapses with postsynaptic densities and vesicle-loaded synapses in the mutant null cortex. The overall pathology in the null mice suggested cortical dyslamination most likely because of mislocalization of late-born neurons, with an admixture of those carrying suboptimally developed axons and dendrites with reduced functional synapses with normal neurons. Our study suggests that LGI1 has a role in regulating cortical development, which is increasingly becoming recognized as one of the causes of idiopathic epilepsy.


Subject(s)
Malformations of Cortical Development/genetics , Malformations of Cortical Development/pathology , Proteins/genetics , Animals , Axons/ultrastructure , Cell Movement/genetics , Dendritic Spines/ultrastructure , Gene Deletion , Homozygote , Intracellular Signaling Peptides and Proteins , Mice , Neurites/pathology , Synapses/ultrastructure
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